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Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. This phase I trial is studying the side effects and best dose of tipifarnib in treating patients with relapsed or refractory acute myeloid leukemia

Cohorts of 3-6 patients receive escalating doses of tipifarnib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 6 months for survival.

PROJECTED ACCRUAL: A total of 20-30 patients will be accrued for this study.

MTD defined as the highest dose level in which six patients have been evaluated for toxicity with no more than one patient experiencing dose limiting toxicity (DLT) assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: 28 days ]

The toxicities observed at each dose level will be summarized in terms of type, severity, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.

Objective tumor response [ Time Frame: Up to 6.5 years ]

Will be summarized at each dose level, and the number and percent responding combined across dose levels.

Survival [ Time Frame: From registration to time of death due to any cause, assessed up to 6.5 years ]

Will be summarized with Kaplan-Meier plots.

Time to treatment failure [ Time Frame: From registration to the first observation of disease progression, death due to any cause, or early discontinuation of treatment, assessed up to 6.5 years ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Bone marrow and peripheral blood studies must be available for confirmation of diagnosis; cytogenetics, flow cytometry, and molecular studies (such as fms-related tyrosine kinase 3 [Flt-3] status) will be obtained as per standard practice

Patients with active central nervous system (CNS) leukemia are NOT eligible

Performance status of 60% or greater by the Karnofsky scale

If induction chemotherapy has been attempted, a minimum of 4 weeks must have elapsed since the completion of prior chemotherapy in order to be eligible for this study; hydroxyurea for control of blasts is not counted as chemotherapy, and may be given up until 24 hours before starting R115777

Patients may have had prior autologous transplant; they must be at least 100 days post transplant, and have had recovery of their counts with ANC > 1000 and platelets greater than 100K at some point post transplant, and be without active CMV or fungal disease

Patients may have received prior radiation therapy as part of a transplant conditioning regimen; radiotherapy must have been completed at least 100 days prior to starting on R115777

There are no minimum hematological parameter requirements prior to the first two cycles of R115777, as patients with AML and MDS are understood to have low ANC and platelet counts when the disease is active; however, patients with WBC greater than 30,000 will receive hydroxyurea to reduce WBC to below 30,000 at which point they may begin treatment with R115777

Any condition causing inability to swallow pills given by mouth will render patients ineligible for the trial

There must be no plans for the patient to receive concurrent hormonal, biologic, or radiation therapy

Patients eligible, at the time of starting the drug, for curative therapeutic approaches (such as allogeneic transplant) are not eligible for the trial; however, patients who achieve CR or PR as a result of R115777 may go on to allogeneic transplant

Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

Prior to the first patient registration, the notification of institutional review board approval for this study must be provided to the Data Coordinating Center at City of Hope

Antacids are allowed but must not be taken concurrently with R115777; (there must be at least 2 hours between antacid intake and R115777 dosing)

Pregnant or lactating women are excluded from this trial; all patients of child-bearing potential, both male and female, must be advised to practice adequate contraception; premenopausal women must have a negative pregnancy test prior to entry on this study